Method and device for electrospray ionization

ABSTRACT

The present invention relates to electrospray device and a method for heating a liquid in said electrospray device. The device comprising a liquid source ( 3 ), a mass analyser ( 5 ), and inlet plate ( 17 ) with an inlet orifice ( 19 ), liquid inlet means such as a capillary tube ( 9 ) having a spray tip ( 11 ) for emitting liquid from said liquid source ( 3 ) and it further comprises microwave energy emitting means ( 21 ) between said spray tip ( 11 ) and said mass analyser ( 5 ) for heating said liquid.

FIELD OF THE INVENTION

The present invention relates to devices and methods for assistingionisation of liquid samples for subsequent mass spectrometer analysis.

PRIOR ART

Mass spectrometers are often used to analyse the masses of components ofliquid samples obtained from analysis devices such as liquidchromatographs. Mass spectrometers require that the component samplethat is to be analysed be provided in the form of free ions and it isusually necessary to evaporate the liquid samples in order to produce avapour of ions. This is commonly achieved by using electrosprayionisation. In electrospray ionisation (ESI) a spray is generated byapplying a voltage (in the order of 2-3 kV) to a hollow needle throughwhich the liquid sample can freely flow. The inlet orifice to the massspectrometer is given a lower potential, for example 0V, and anelectrical field is generated from the tip of the needle to the orificeof the mass spectrometer. The electrical field attracts the positivelycharge species in the fluid which accumulate in the meniscus of theliquid at the tip of the needle. The negatively charged species in thefluid are neutralised. This meniscus extends towards the oppositelycharged orifice and forms a “Taylor cone”. When the attraction betweenthe charged species and the orifice exceeds the surface tension of thetip of the Taylor cone, droplets break free from the Taylor cone and flyin the direction of the electrical field lines towards the orifice.During the flight towards the orifice the liquid in the dropletsevaporates and the net positive charge in the droplet increases. As thenet charge increases, the columbic repulsion between the like charges inthe droplet also increases. When the repulsion force between these likecharges exceeds the liquid surface tension in the droplet, the dropletbursts into several smaller droplets. The liquid in these droplets inturn evaporates and these droplets also burst. This occurs several timesduring the flight towards the orifice.

There are two theories about how the analytes in the liquid enter thevapour phase as free ions. In the first theory, known a the iondesorption method, it is assumed that when the droplet size reduces to acertain small volume, the repulsion between the charged molecules in thedroplet will cause the molecules to penetrate the liquid surface andenter the vapour phase. As the droplets continue to shrink, more andmore molecules enter the vapour phase.

In the second theory, known as the charged residue mechanism, it isassumed that there comes a stage where each droplet is very small andeach one only contains one analyte molecule. As the last molecules ofsolvent, usually water, evaporate from the droplet, the excess ofpositive charges in the water is transferred to the analyte moleculewhich is now in the vapour phase. For the purposes of the invention, itdoes not matter which theory is correct. A problem with electrosprayionisation is that at high flow rates (e.g. over about 10 microlitersper minutes) the average size of the droplets increases. Many of thesedroplets hit the inlet plate and are neutralised before the molecules ofinterest have entered the vapour phase. This means that these moleculeswill not be analysed which leads to reduced sensitivity.

U.S. Pat. No. 4,935,624 teaches an improved method and apparatus forforming ions at atmospheric pressure from a liquid and for introducingthe ions into a mass analyser. It attempts to overcome the disadvantageof electrospray ionisation when used for flows much greater than 10microliters per minute e.g. up to about 2000 microliters per minute. Inthis document, the apparatus for forming ions comprises a capillary tubethat receives the liquid from a liquid chromatograph, and a thermalenergy means for directly or indirectly heating the liquid in thecapillary tube. The thermal energy means could be provided byelectrically resistive heating, piezoelectric heating, ultrasonicheating, infrared heating, microwave heating and conduction from gasheating. The addition of extra heat disperses the droplets into a finemist. This device suffers from the disadvantage that the heating of theliquid takes place in a capillary tube which means that heating of thedroplets is not homogeneous—as the capillary wall inevitably is warmsome of the heating takes place from the outside of the droplet towardsthe inside of the droplet due to the contact between the droplet and thewarm capillary wall. Therefore some of the liquid may boil while therest of the liquid is barely warmed. This is disadvantageous because ifthe liquid boils then the electrochemical reaction that generates theexcess of positive charges which promotes the spray will not occur,while if the liquid is barely heated then the droplets will notevaporate quickly enough on their flights to the orifice.

SUMMARY OF THE INVENTION

The purpose of the present invention is to provide devices and methodswhich overcome the disadvantages of the prior art devices and methodsfor assisting the ionisation of liquid samples for subsequent massspectrometer analysis. This is achieved by means of a device having thecharacterising features of claim 1 and a method having thecharacterising features of claim 4.

In particular, in a first embodiment of a device in accordance with thepresent invention, a microwave-emitting device is positioned between thespray tip of a tube that receives the liquid from a source such as aliquid chromatograph and the target orifice. In this way the dropletsare heated in a homogeneous way by the microwaves emitted from themicrowave-emitting device.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 shows a diagrammatic view of a first embodiment of a device inaccordance with the present invention; and,

FIG. 2 shows diagrammatically different possible positions for amicrowave-emitting means in accordance with the invention.

DETAILED DESCRIPTION OF EMBODIMENTS ILLUSTRATING THE INVENTION

FIG. 1 shows diagrammatically an electrospray device 1 in accordancewith the invention in which practical details which are not related tothe present invention are omitted form the sake of ease and clarity ofillustration. In the electrospray device 1, liquid that containmolecules to be analysed, and issuing from a liquid source, for examplea liquid chromatograph 3, is analysed by a mass analyser such as a massspectrometer 5. The liquid is led from the liquid chromatograph 3through an outlet tube 7 that leads to a discharge tube 9 for the massspectrometer 5. This discharge tube 9 is typically in the form of acapillary tube 9 which has an spray tip 11 which projects into theionisation chamber 13 of the device 1. The capillary tube 9 is connectedto an electrical potential of, for example, 3000 Volts. The ionisationchamber 13 is separated from the mass spectrometer vacuum chamber 15 byan inlet plate 17 containing an inlet orifice 19 at a lower potential,for example, earth potential. Electrically charged liquid drops leavethe spray tip 11 of capillary tube 9 and evaporate as they traveltowards the inlet orifice 19. This leads to ionisation of the samplemolecules in the liquid. A microwave emitting means, such as a microwavehead 21, is positioned in the ionisation chamber 13 close to the spraytip 11 of said capillary tube 9. The microwave head 21 is alignedtowards the liquid issuing from said spray tip 11 of said capillary tube9. The microwave head 21 can be controlled by control means 23 to emitmicrowaves of the appropriate frequency and power needed to heat up theliquid issuing from the spray tip 11 of the capillary tube 9 so that theliquid evaporates more rapidly. In the event that the liquid is anaqueous solution then microwaves having a frequency of 2.45 GHz may beused. Other liquids that have a high dipole moment will also increasetheir thermal energy when exposed to microwave radiation. As themicrowave energy penetrates the liquid, it heats up the liquidhomogeneously, thereby avoiding that some of the liquid boils while someof the liquid remains cold.

FIG. 2 shows diagrammatically a number of different possible positionsfor a microwave-emitting means. In a first position, shown in solidlines the microwave-emitting means 21′ is positioned in front of, and toone side of, the spray tip 11 of the capillary tube. In this position itdirects microwave energy to the droplets at an angle which substantiallyperpendicular to the line of flight of the liquid droplets. This meansthat each droplet can only be exposed to microwave radiation when itpasses directly in front of the microwave-emitting means. In a secondposition, shown by dashed lines, the microwave-emitting means 21″ ispositioned behind the spray tip 11 of the capillary tube 9 and points inthe direction towards the orifice. This means that droplets can bealmost continuously exposed to microwave energy as they fly towards theorifice. The intensity of the microwave energy and the size of thedroplets decrease as the droplets approach the orifice. This ensuresthat the droplets are heated for a sufficiently long time to cause thefluid to evaporate while at the same time the risk of boiling theprogressively smaller droplets is reduced. In a third position, shown bydotted lines, a microwave-emitting means 21′″ is positioned near to theinlet plate 17 and faces back towards the capillary tube 9. In thisposition, the intensity of the microwave energy that can be received bydroplets increases as the droplets approach the inlet plate 17 andorifice 19. This ensures that all droplets evaporate before they reachthe inlet plate 17. It is of course conceivable to use a plurality ofmicrowave-emitting means 21-21′″ placed in any or all of the abovementioned positions or even other positions in order to obtain theadvantages provided by the various positions. It is also possible toarrange that micro-wave energy is emitted in a continuous mode or in apulsed mode or as a pulsed mode superimposed on a continuous mode.

When the microwave-emitting means is positioned in the vicinity of thecapillary tube 9, it is preferable positioned as close as possible tothe spray tip 11 of capillary tube 9 in order to act as efficiently aspossible, due regard however being paid to avoiding large disturbancesin the electric field between the capillary tube 9 and the inlet plate17. In practice, a microwave head 21 with 0 Volts applied to it can beintroduced to within about 1 cm from the spray tip 11 at 3000 Voltswithout affecting the quality of the spectra of the mass spectrometer.

While the invention has been illustrated by examples showing a microwavehead inside the ionisation chamber, it is of course conceivable to havethe microwave head outside the ionisation chamber and to use a waveguideto lead the microwaves to one or more microwave-emitting means insidethe ionisation chamber.

While the invention has been illustrated by an example in which theliquid to be analysed comes from a liquid chromatograph, it is possibleto apply the device and method of the present invention to any ionisableliquid, irrespective of its source.

Possible Other Claim Formulations

Electrospray device comprising a spray means (11) for producing liquiddroplets and a target (19) characterised that it comprises microwaveenergy emitting means (21) for heating said liquid wherein saidmicrowave-emitting means is positioned between said spray means (11) andsaid target (19).

Electrospray device in accordance with claim 1 comprising a liquidsource (3), an inlet plate (17) with an inlet orifice (19), liquid inletmeans such as a capillary tube (9) having an spray tip (11) for emittingliquid from said liquid source (3) wherein said microwave energyemitting means (21) for heating said liquid is positioned between saidspray tip (11) and said inlet plate.

What is claimed is:
 1. In an electrospray device comprising a liquidsource (3) and liquid inlet means (9) having an spray tip (11) foremitting liquid droplets from said liquid source (3) the improvementcomprising including microwave energy emitting means (21) for heatingsaid liquid after it has left said spray tip (11).
 2. The electrospraydevice of claim 1 wherein said microwave energy emitting means is amicrowave head (21).
 3. The electrospray device of claim 1 wherein saidmicrowave energy emitting means (23) is positioned between said spraytip (11) and an inlet orifice (19).
 4. The electrospray device of claim1 which includes a plurality of microwave energy emitting means(21-21″).
 5. In a method for heating a liquid in an electrospray devicewherein said liquid issues from an outlet end (11) of a capillary tube(9) and is directed to an inlet orifice (19) of an inlet plate (17) of amass analyser (5) the improvement comprising heating said liquid bymicrowave energy when said liquid is between said spray tip (11) andsaid mass analyser (5).
 6. The method of claim 5 wherein said microwaveenergy is from a microwave energy emitting means (21) which ispositioned to direct microwave energy to droplets after they have leftsaid spray tip (11).
 7. The method of claim 5 wherein said microwaveenergy is from at least two microwave energy emitting means (21-21″).